Multi-arylated heteroarenes and bi-phenyls are important motifs in a number of industries, such as organic semi-conductors and medicinal chemistry. Biphenyls are classically synthesized by transition metal catalyzed cross-couplings. Typically, non-symmetric, multi-arylated thiophenes and furans are prepared either by cyclization or transition metal catalyzed cross-coupling reactions. The latter strategy is more attractive as it allows for late stage functionalization and facilitates the synthesis of compound libraries. It is, however, more challenging to regioselectively functionalize each position on the heteroarene with cross-coupling. These synthetic steps tend to require a stoichiometric amount of organometallic reagent, and therefore generate heavy metallic waste, and can be impractical in terms of air- and moisture-sensitivity and long reaction times. To facilitate access to multi-arylated thiophenes and furans, we have developed cross-coupling methodologies that utilize the different facets of a carboxylic acid/ester functional group to regioselectively arylate thiophene and furan. This approach is both greener than previously reported methodologies and very practical in its relative simplicity. First, a double decarboxylative cross-coupling (DCC) route is devised as an effective strategy for quick access to non-symmetric, di-arylated thiophenes. Second, an expanded route utilizing directed halogenation, DCC, and Suzuki-Miyaura cross-couplings is developed in order to access tetra-arylated thiophene, tetra-arylated furan, as well as the various isomers of di- and tri-arylated thiophenes and furans. Of the cross-couplings utilized in these modular routes, DCC has the advantage of avoiding the use of organometallic reagents to generate the nucleophilic coupling partner. Unfortunately, this reaction is low yielding with un-activated benzoic acids, and requires hazardous solvents, high temperatures and long reaction times with these substrates. To access biphenyl bonds with a cross-coupling reaction that minimizes organometallic waste, avoids hazardous solvents and is done under relatively mild condition, a first-generation deselenative cross-coupling was also developed.